Phase I evaluation of docetaxel and topotecan for patients with advanced solid tumors

Cancer. 2004 May 15;100(10):2240-5. doi: 10.1002/cncr.20238.

Abstract

Background: The authors administered a combination of docetaxel and topotecan with granulocyte-colony-stimulating factor (G-CSF) support in a Phase I study to define the maximum tolerated dose (MTD) of this regimen.

Methods: Patients with advanced-stage solid tumors were eligible for this trial if they had a Zubrod performance status of </= 2 and normal renal, hepatic, and bone marrow function. No previous therapy with taxanes or topoisomerase inhibitors was allowed. The authors administered both docetaxel and topotecan in a dose-escalated manner until the MTD was reached. Docetaxel was given on Day 1 of each cycle before topotecan, which was administered intravenously on Days 1-3. Granulocyte-colony-stimulating factor (G-CSF) support with 5 microg/kg subcutaneous injections was initiated on Day 4 and continued until the absolute granulocyte count recovered to 2000/microL. Treatment cycles were repeated every 21 days.

Results: Of the 11 patients enrolled in the current study, all were evaluable for toxicity and 10 were evaluable for response. A median of three treatment cycles was received (range, one to nine treatment cycles). The dose-limiting toxicity was Grade 4 (according to the National Cancer Institute Common Toxicity Criteria for Adverse Events [version 2.0]). neutropenia with fever. The MTD was 75 mg/m2 of docetaxel on Day 1 and 1.4 mg/m2 of topotecan on Days 1-3. There was one complete response and one partial response in patients with nasopharyngeal carcinoma and one partial response in a patient with small cell lung carcinoma (SCLC). The response durations were 24 weeks, 29 weeks, and >/= 244 weeks, respectively. At the time of last follow-up, both patients with nasopharyngeal carcinoma were still alive at 241 weeks and 244 weeks, respectively.

Conclusions: This trial demonstrated that a regimen of docetaxel and topotecan with G-CSF support was generally well tolerated and had promising activity in patients with nasopharyngeal and SCLC.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Docetaxel
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Taxoids / administration & dosage
  • Topotecan / administration & dosage
  • Treatment Outcome

Substances

  • Taxoids
  • Docetaxel
  • Topotecan